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Comparison of the direct effects of human adipose- and bone-marrow-derived stem cells on postischemic cardiomyoblasts in an in vitro simulated ischemia-reperfusion model.

ABSTRACT: Regenerative therapies hold a promising and exciting future for the cure of yet untreatable diseases, and mesenchymal stem cells are in the forefront of this approach. However, the relative efficacy and the mechanism of action of different types of mesenchymal stem cells are still incompletely understood. We aimed to evaluate the effects of human adipose- (hASC) and bone-marrow-derived stem cells (hBMSCs) and adipose-derived stem cell conditioned media (ACM) on the viability of cardiomyoblasts in an in vitro ischemia-reperfusion (I-R) model. Flow cytometric viability analysis revealed that both cell treatments led to similarly increased percentages of living cells, while treatment with ACM did not (I-R model: 12.13 ± 0.75%; hASC: 24.66 ± 2.49%; hBMSC: 25.41 ± 1.99%; ACM: 13.94 ± 1.44%). Metabolic activity measurement (I-R model: 0.065 ± 0.033; hASC: 0.652 ± 0.089; hBMSC: 0.607 ± 0.059; ACM: 0.225 ± 0.013; arbitrary units) and lactate dehydrogenase assay (I-R model: 0.225 ± 0.006; hASC: 0.148 ± 0.005; hBMSC: 0.146 ± 0.004; ACM: 0.208 ± 0.009; arbitrary units) confirmed the flow cytometric results while also indicated a slight beneficial effect of ACM. Our results highlight that mesenchymal stem cells have the same efficacy when used directly on postischemic cells, and differences found between them in preclinical and clinical investigations are rather related to other possible causes such as their immunomodulatory or angiogenic properties.

SUBMITTER: Szepes M

PROVIDER: S-EPMC3703900 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Comparison of the direct effects of human adipose- and bone-marrow-derived stem cells on postischemic cardiomyoblasts in an in vitro simulated ischemia-reperfusion model.

Szepes Mónika M Benkő Zsolt Z Cselenyák Attila A Kompisch Kai Michael KM Schumacher Udo U Lacza Zsombor Z Kiss Levente L

Stem cells international 20130619

Regenerative therapies hold a promising and exciting future for the cure of yet untreatable diseases, and mesenchymal stem cells are in the forefront of this approach. However, the relative efficacy and the mechanism of action of different types of mesenchymal stem cells are still incompletely understood. We aimed to evaluate the effects of human adipose- (hASC) and bone-marrow-derived stem cells (hBMSCs) and adipose-derived stem cell conditioned media (ACM) on the viability of cardiomyoblasts i ...[more]

PMID: 23853609

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Project description:Search for new cardioprotective therapies is of great importance since no cardioprotective drugs are available on the market. In line with this need, several natural biomolecules have been extensively tested for their potential cardioprotective effects. Previously, we have shown that biglycan, a member of a diverse group of small leucine-rich proteoglycans, enhanced the expression of cardioprotective genes and decreased ischemia/reperfusion-induced cardiomyocyte death via a TLR-4 dependent mechanism. Therefore, in the present study we aimed to test whether decorin, a small leucine-rich proteoglycan closely related to biglycan, could exert cardiocytoprotection and to reveal possible downstream signaling pathways. Methods: Primary cardiomyocytes isolated from neonatal and adult rat hearts were treated with 0 (Vehicle), 1, 3, 10, 30 and 100 nM decorin as 20 h pretreatment and maintained throughout simulated ischemia and reperfusion (SI/R). In separate experiments, to test the mechanism of decorin-induced cardio protection, 3 nM decorin was applied in combination with inhibitors of known survival pathways, that is, the NOS inhibitor L-NAME, the PKG inhibitor KT-5823 and the TLR-4 inhibitor TAK-242, respectively. mRNA expression changes were measured after SI/R injury. Results: Cell viability of both neonatal and adult cardiomyocytes was significantly decreased due to SI/R injury. Decorin at 1, 3 and 10 nM concentrations significantly increased the survival of both neonatal and adult myocytes after SI/R. At 3nM (the most pronounced protective concentration), it had no effect on apoptotic rate of neonatal cardiac myocytes. No one of the inhibitors of survival pathways (L-NAME, KT-5823, TAK-242) influenced the cardiocytoprotective effect of decorin. MYND-type containing 19 (Zmynd19) and eukaryotic translation initiation factor 4E nuclear import factor 1 (Eif4enif1) were significantly upregulated due to the decorin treatment. In conclusion, this is the first demonstration that decorin exerts a direct cardiocytoprotective effect possibly independent of NO-cGMP-PKG and TLR-4 dependent survival signaling.

Dataset Information

Comparison of the direct effects of human adipose- and bone-marrow-derived stem cells on postischemic cardiomyoblasts in an in vitro simulated ischemia-reperfusion model.

Publications

Comparison of the direct effects of human adipose- and bone-marrow-derived stem cells on postischemic cardiomyoblasts in an in vitro simulated ischemia-reperfusion model.

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